scholarly journals Metformin does not compromise energy status in human skeletal muscle at rest or during acute exercise: A randomised, crossover trial

2019 ◽  
Vol 7 (23) ◽  
Author(s):  
Jonas M. Kristensen ◽  
Christian Lillelund ◽  
Rasmus Kjøbsted ◽  
Jesper B. Birk ◽  
Nicoline R. Andersen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Acute Exercise ◽  
Crossover Trial ◽  
Energy Status

scholarly journals Endurance training reduces the contraction-induced interleukin-6 mRNA expression in human skeletal muscle

2004 ◽  
Vol 287 (6) ◽  
pp. E1189-E1194 ◽  
Author(s):  
Christian P. Fischer ◽  
Peter Plomgaard ◽  
Anne K. Hansen ◽  
Henriette Pilegaard ◽  
Bengt Saltin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Muscle Glycogen ◽  
Human Skeletal Muscle ◽  
Acute Exercise ◽  
Glycogen Content ◽  
Knee Extensor ◽  
Exercise Induced ◽  
Response To Exercise ◽  
Resting Muscle

Contracting skeletal muscle expresses large amounts of IL-6. Because 1) IL-6 mRNA expression in contracting skeletal muscle is enhanced by low muscle glycogen content, and 2) IL-6 increases lipolysis and oxidation of fatty acids, we hypothesized that regular exercise training, associated with increased levels of resting muscle glycogen and enhanced capacity to oxidize fatty acids, would lead to a less-pronounced increase of skeletal muscle IL-6 mRNA in response to acute exercise. Thus, before and after 10 wk of knee extensor endurance training, skeletal muscle IL-6 mRNA expression was determined in young healthy men ( n = 7) in response to 3 h of dynamic knee extensor exercise, using the same relative workload. Maximal power output, time to exhaustion during submaximal exercise, resting muscle glycogen content, and citrate synthase and 3-hydroxyacyl-CoA dehydrogenase enzyme activity were all significantly enhanced by training. IL-6 mRNA expression in resting skeletal muscle did not change in response to training. However, although absolute workload during acute exercise was 44% higher ( P < 0.05) after the training period, skeletal muscle IL-6 mRNA content increased 76-fold ( P < 0.05) in response to exercise before the training period, but only 8-fold ( P < 0.05, relative to rest and pretraining) in response to exercise after training. Furthermore, the exercise-induced increase of plasma IL-6 ( P < 0.05, pre- and posttraining) was not higher after training despite higher absolute work intensity. In conclusion, the magnitude of the exercise-induced IL-6 mRNA expression in contracting human skeletal muscle was markedly reduced by 10 wk of training.

Exercise training increases branched-chain oxoacid dehydrogenase kinase content in human skeletal muscle

2007 ◽  
Vol 293 (3) ◽  
pp. R1335-R1341 ◽  
Author(s):  
Krista R. Howarth ◽  
Kirsten A. Burgomaster ◽  
Stuart M. Phillips ◽  
Martin J. Gibala
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Protein Content ◽  
Human Skeletal Muscle ◽  
Acute Exercise ◽  
Citrate Synthase ◽  
Muscle Protein ◽  
Moderate Intensity ◽  
Main Effect ◽  
Branched Chain

The branched-chain oxoacid dehydrogenase complex (BCOAD) is rate determining for the oxidation of branched-chain amino acids (BCAAs) in skeletal muscle. Exercise training blunts the acute exercise-induced activation of BCOAD (BCOADa) in human skeletal muscle (McKenzie S, Phillips SM, Carter SL, Lowther S, Gibala MJ, Tarnopolsky MA. Am J Physiol Endocrinol Metab 278: E580–E587, 2000); however, the mechanism is unknown. We hypothesized that training would increase the muscle protein content of BCOAD kinase, the enzyme responsible for inactivation of BCOAD by phosphorylation. Twenty subjects [23 ± 1 yr; peak oxygen uptake (V̇o2peak) = 41 ± 2 ml·kg−1·min−1] performed 6 wk of either high-intensity interval or continuous moderate-intensity training on a cycle ergometer ( n = 10/group). Before and after training, subjects performed 60 min of cycling at 65% of pretraining V̇o2peak, and needle biopsy samples (vastus lateralis) were obtained before and immediately after exercise. The effect of training was demonstrated by an increased V̇o2peak, increased citrate synthase maximal activity, and reduced muscle glycogenolysis during exercise, with no difference between groups (main effects, P < 0.05). BCOADa was lower after training (main effect, P < 0.05), and this was associated with a ∼30% increase in BCOAD kinase protein content (main effect, P < 0.05). We conclude that the increased protein content of BCOAD kinase may be involved in the mechanism for reduced BCOADa after exercise training in human skeletal muscle. These data also highlight differences in models used to study the regulation of skeletal muscle BCAA metabolism, since exercise training was previously reported to increase BCOADa during exercise and decrease BCOAD kinase content in rats (Fujii H, Shimomura Y, Murakami T, Nakai N, Sato T, Suzuki M, Harris RA. Biochem Mol Biol Int 44: 1211–1216, 1998).

Skeletal muscle adaptations to exercise are not influenced by metformin treatment in humans: secondary analyses of two randomised, clinical trials.

2021 ◽  
Author(s):  
Nanna Skytt Pilmark ◽  
Laura Oberholzer ◽  
Jens Frey Halling ◽  
Jonas M. Kristensen ◽  
Christina Pedersen Bønding ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Exercise Training ◽  
Human Skeletal Muscle ◽  
Acute Exercise ◽  
Metformin Treatment ◽  
Ampk Activation ◽  
Double Blind ◽  
Parallel Group ◽  
Exercise Induced

Metformin and exercise both improve glycemic control, but in vitro studies have indicated that an interaction between metformin and exercise occurs in skeletal muscle, suggesting a blunting effect of metformin on exercise training adaptations. Two studies (a double-blind, parallel-group, randomized clinical trial conducted in 29 glucose-intolerant individuals and a double-blind, cross-over trial conducted in 15 healthy lean males) were included in this paper. In both studies, the effect of acute exercise +/- metformin treatment on different skeletal muscle variables, previously suggested to be involved in a pharmaco-physiological interaction between metformin and exercise, was assessed. Furthermore, in the parallel-group trial, the effect of 12 weeks of exercise training was assessed. Skeletal muscle biopsies were obtained before and after acute exercise and 12 weeks of exercise training, and mitochondrial respiration, oxidative stress and AMPK activation was determined. Metformin did not significantly affect the effects of acute exercise or exercise training on mitochondrial respiration, oxidative stress or AMPK activation, indicating that the response to acute exercise and exercise training adaptations in skeletal muscle is not affected by metformin treatment. Further studies are needed to investigate whether an interaction between metformin and exercise is present in other tissues, e.g. the gut. Trial registration: ClinicalTrials.gov (NCT03316690 and NCT02951260). Novelty bullets • Metformin does not affect exercise-induced alterations in mitochondrial respiratory capacity in human skeletal muscle • Metformin does not affect exercise-induced alterations in systemic levels of oxidative stress nor emission of reactive oxygen species from human skeletal muscle • Metformin does not affect exercise-induced AMPK activation in human skeletal muscle

scholarly journals Contractile activity-specific transcriptome response to acute endurance exercise and training in human skeletal muscle

2019 ◽  
Vol 316 (4) ◽  
pp. E605-E614 ◽  
Author(s):  
Daniil V. Popov ◽  
Pavel A. Makhnovskii ◽  
Elena I. Shagimardanova ◽  
Guzel R. Gazizova ◽  
Evgeny A. Lysenko ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factors ◽  
Human Skeletal Muscle ◽  
Acute Exercise ◽  
Contractile Activity ◽  
Vastus Lateralis ◽  
Aerobic Exercise Training ◽  
Vastus Lateralis Muscle ◽  
Transcriptome Response ◽  
The One

Reduction in daily activity leads to dramatic metabolic disorders, while regular aerobic exercise training is effective for preventing this problem. The purpose of this study was to identify genes that are directly related to contractile activity in human skeletal muscle, regardless of the level of fitness. Transcriptome changes after the one-legged knee extension exercise in exercised and contralateral nonexercised vastus lateralis muscle of seven men were evaluated by RNA-seq. Transcriptome change at baseline after 2 mo of aerobic training (5/wk, 1 h/day) was evaluated as well. Postexercise changes in the transcriptome of exercised muscle were associated with different factors, including circadian oscillations. To reveal transcriptome response specific for endurance-like contractile activity, differentially expressed genes between exercised and nonexercised muscle were evaluated at 1 and 4 h after the one-legged exercise. The contractile activity-specific transcriptome responses were associated only with an increase in gene expression and were regulated mainly by CREB/ATF/AP1-, MYC/MAX-, and E2F-related transcription factors. Endurance training-induced changes (an increase or decrease) in the transcriptome at baseline were more pronounced than transcriptome responses specific for acute contractile activity. Changes after training were associated with widely different biological processes than those after acute exercise and were regulated by different transcription factors (IRF- and STAT-related factors). In conclusion, adaptation to regular exercise is associated not only with a transient (over several hours) increase in expression of many contractile activity-specific genes, but also with a pronounced change (an increase or decrease) in expression of a large number of genes under baseline conditions.

Regulation of PDH activity and isoform expression: diet and exercise

2003 ◽  
Vol 31 (6) ◽  
pp. 1274-1280 ◽  
Author(s):  
S.J. Peters
Keyword(s):  
Skeletal Muscle ◽  
Nutritional Status ◽  
Human Skeletal Muscle ◽  
Acute Exercise ◽  
Pyruvate Dehydrogenase Complex ◽  
Energy Charge ◽  
Relative Activity ◽  
Signal Energy ◽  
Diet And Exercise ◽  
Product Accumulation

During exercise in human skeletal muscle, the proportion of carbohydrate derived acetyl-CoA is determined at least in part by the activity of the PDH (pyruvate dehydrogenase) complex. Inhibition of the complex is achieved through reversible phosphorylation of the E1 subunit by a family of PDH kinase isoforms (PDK1–4) while dephosphorylation and activation of the complex is catalysed by a pair of intrinsic PDH phosphatases (PDP1 and 2). In general, the relative activity of the kinases and phosphatases is determined by a host of intramitochondrial effectors which signal energy charge, substrate and product accumulation, muscle contraction and nutritional status. This review focuses on advances in our understanding in human skeletal muscle of the regulatory signals and changes in gene expression which are important during acute exercise and exercise training, as well as in prolonged situations of altered nutritional status.

Effect of acute exercise and exercise training on VEGF splice variants in human skeletal muscle

2004 ◽  
Vol 287 (2) ◽  
pp. R397-R402 ◽  
Author(s):  
Lotte Jensen ◽  
Henriette Pilegaard ◽  
P. Darrell Neufer ◽  
Ylva Hellsten
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Human Skeletal Muscle ◽  
Acute Exercise ◽  
Splice Variants ◽  
Knee Extensor ◽  
Vastus Lateralis Muscle ◽  
Mrna Levels ◽  
Vegf Mrna ◽  
Exercise Induced

The present study investigated the effect of an acute exercise bout on the mRNA response of vascular endothelial growth factor (VEGF) splice variants in untrained and trained human skeletal muscle. Seven habitually active young men performed one-legged knee-extensor exercise training at an intensity corresponding to ∼70% of the maximal workload in an incremental test five times/week for 4 wk. Biopsies were obtained from the vastus lateralis muscle of the trained and untrained leg 40 h after the last training session. The subjects then performed 3 h of two-legged knee-extensor exercise, and biopsies were obtained from both legs after 0, 2, 6, and 24 h of recovery. Real-time PCR was used to examine the expression of VEGF mRNA containing exon 1 and 2 (all VEGF isoforms), exon 6 or exon 7, and VEGF165mRNA. Acute exercise induced an increase ( P < 0.05) in total VEGF mRNA levels as well as VEGF165and VEGF splice variants containing exon 7 at 0, 2, and 6 h of recovery. The increase in VEGF mRNA was higher in the untrained than in the trained leg ( P < 0.05). The results suggest that in human skeletal muscle, acute exercise increases total VEGF mRNA, an increase that appears to be explained mainly by an increase in VEGF165mRNA. Furthermore, 4 wk of training attenuated the exercise-induced response in skeletal muscle VEGF165mRNA.

Exercise adaptation attenuates VEGF gene expression in human skeletal muscle

2000 ◽  
Vol 279 (2) ◽  
pp. H772-H778 ◽  
Author(s):  
R. S. Richardson ◽  
H. Wagner ◽  
S. R. D. Mudaliar ◽  
E. Saucedo ◽  
R. Henry ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Human Skeletal Muscle ◽  
Acute Exercise ◽  
Vastus Lateralis ◽  
Northern Analysis ◽  
Endothelial Cell Proliferation ◽  
Vastus Lateralis Muscle ◽  
Mrna Levels ◽  
Exercise Adaptation

Angiogenesis is a component of the multifactoral adaptation to exercise training, and vascular endothelial growth factor (VEGF) is involved in extracellular matrix changes and endothelial cell proliferation. However, there is limited evidence supporting the role of VEGF in the exercise training response. Thus we studied mRNA levels of VEGF, using quantitative Northern analysis, in untrained and trained human skeletal muscle at rest and after a single bout of exercise. Single leg knee-extension provided the acute exercise stimulus and the training modality. Four biopsies were collected from the vastus lateralis muscle at rest in the untrained and trained conditions before and after exercise. Training resulted in a 35% increase in muscle oxygen consumption and an 18% increase in number of capillaries per muscle fiber. At rest, VEGF/18S mRNA levels were similar before (0.38 ± 0.04) and after (1.2 ± 0.4) training. When muscle was untrained, acute exercise greatly elevated VEGF/18S mRNA levels (16.9 ± 6.7). The VEGF/18S mRNA response to acute exercise in the trained state was markedly attenuated (5.4 ± 1.3). These data support the concept that VEGF is involved in exercise-induced skeletal muscle angiogenesis and appears to be subject to a negative feedback mechanism as exercise adaptations occur.

scholarly journals PL-008 Adaptation of skeletal muscle to aerobic exercise: specific transcriptome response to acute exercise and training

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Daniil Popov ◽  
Pavel Makhnovskii ◽  
Evgeny Lysenko ◽  
Olga Vinogradova
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Circadian Rhythm ◽  
Human Skeletal Muscle ◽  
Acute Exercise ◽  
Aerobic Training ◽  
Contractile Activity ◽  
Training Programme ◽  
Specific Response ◽  
Transcriptome Response

Objective Variety of processes including circadian rhythm and systemic factors affect expression of many genes in skeletal muscle during a day. Therefore, post-exercise gene expression depends on many factors: contractile activity per seas well as circadian rhythm, nerve activity, concentration of different substances in blood, feeding and fasting. In our study, we investigated specific for contractile activity changes in the transcriptome in untrained and trained (after an aerobic training programme) human skeletal muscle. The second goal was to examine effect of aerobic training on gene expression in muscle in basal state. Methods Seven untrained males performed the one-legged knee extension exercise (for 60 min) with the same relative intensity before and after a 2 month aerobic training programme (1 h/day, 5/week). Biopsy samples were taken at rest (basal state, 48 h after the previous exercise), 1 and 4 h after one-legged exercise from m. vastus lateralisof either leg. This approach allowed us to evaluate specific changes in the transcriptome associated with contractile activity. RNA­sequencing (84 samples in total; ~42 million reads/sample) was performed by HiSeq 2500 (Illumina). Results Two months aerobic training increased the aerobic capacity of the knee-extensor muscles (power at anaerobic threshold in incremental one-legged and cycling tests), the maximum rate of ADP-stimulated mitochondrial respiration in permeabilized muscle fibres and amounts of oxidative phosphorylation proteins. After one-legged exercise, expression of many genes was changed in exercised muscle (~1500) as well as in non-exercised muscle (~400). Pronounced changes in gene expression in non-exercised muscle may be associated with many factors, including circadian rhythm (result of GO analysis). To examine transcriptome changes specific for contractile activity, the difference in gene expression between legs was examined. In untrained muscle, one-legged exercise changed expression of ~1200 genes specific for contractile activity at each time point. Despite the same relative intensity of one-legged exercise, transcriptomic response in trained muscle was markedly lower (~300 genes) compare to untrained. We observed a strong overlap between transcriptomic responses (~250 genes) and particularly between enriched transcription factor binding sites in promoters of these genes in untrained and trained muscles. These sets of genes and transcription factors play the key role in adaptation of muscle to contractile activity independently on the level of muscular fitness. Surprisingly, 2 months aerobic training changed the expression of more than 1500 genes in basal state. Noteworthy, these genes demonstrated a small overlap (~200 genes) with genes related to specific response to acute exercise. Moreover, these genes were associated with significantly different biological processes than genes related to specific response to acute exercise. Conclusions Specific for contractile activity changes in the transcriptome in untrained and trained human skeletal muscle were revealed for the first time. After 2 month aerobic training, the specific transcriptome response to acute exercise become much less pronounced. A computational approach reveals common transcription factors important for adaptation of both untrained and trained muscle. We found out that adaptation of muscle to aerobic training associates not only with the transitory changes in gene expression after each exercise, but also with the marked changes in transcriptome in basal state. This work was supported by the Russian Science Foundation (14­15­00768).

Sign in / Sign up

Export Citation Format

Share Document